The lymph system contains a network of vessels that carry lymph, a colorless, watery fluid originating from interstitial fluid. The vessels transport excess fluids away from interstitial spaces in body tissue and return it to the bloodstream, while preventing backflow of the lymph fluid. The three main types of lymphatic vessels are lymph capillaries, lymphatics, and lymph ducts. Lymph capillaries join to form larger vessels called lymphatics or lymph veins. These resemble blood-conducting veins but have thinner walls and relatively larger lumen, and they have more valves. In the skin, lymphatics are located in subcutaneous tissue and follow same paths as veins. In the viscera, lymphatics generally follow arteries and form plexuses (networks) around them. At certain locations lymphatics enter lymph nodes. These are small, specialized organs that consist of lymphatic tissue. Lymph is filtered through at least one lymph node before entering the venous circulation (Moore). Lymph nodes act as filters, with an internal honeycomb of connective tissue filled with lymphocytes that collect and destroy e.g. bacteria and viruses. In the node, the lymph is in contact with the blood circulation and about half of the fluid is drained into the blood before it leaves the node via an efferent lymphatic vessel (Renkin). It is an increasingly accepted view that practically all spreading of malignant cells from epithelial tumours first occur through thin fenestrated lymph vessels (by an active mechanism—also used by white blood cells) before entering the general blood circulation via the lympho-venous connections in the lymph nodes. Clusters of lymph nodes are found in the armpits, groins, neck, chest, and abdomen.
Primary tumours or primary tumour areas drain to one or more so-called sentinel lymph nodes, where the sentinel node is defined as the first lymph node, or nodes, to receive lymphatic drainage from a tumour, also known as the “sentinel node concept”. This is also the first site of metastasis and it has been shown in several solid tumour types that the risk of lymph node metastases is almost negligible if the sentinel node is free of tumour cells. The sentinel node can be identified during surgery by injection of a tracer or dye substance around the tumour. These substances are transported in the lymph capillaries and accumulate through phagocytosis by macrophages in the sentinel node(s), thus identifying the tumour draining lymph node(s). The present inventors have recently shown that the sentinel lymph nodes draining a primary tumour are a potential rich source for naturally tumour-reactive T-lymphocytes for in vitro expansion, as the sentinel nodes may contain a substantial amount of T-lymphocytes, that have been sensitized towards tumour-antigens and undergone in vivo expansion in the lymph nodes (Marits et al, manuscript; Karlsson et al, Eur J Urol, accepted).
However, up till now, it has not been known that sequential lymphatic drainage involving a certain individual lymph node applies to metastasis as well, i.e. that for a metastasis one or more lymph nodes draining the metastasis area can be detected.